Abstract

Motivation and attention can have a profound influence on perception, learning and memory. Neuromodulatory systems, especially the noradrenergic (NE) system, co-vary with psychological states to modulate cortical arousal, influence sensory processing and promote synaptic plasticity. There is even some suggestion that the NE system might facilitate functional recovery after brain damage. Post-synaptic effects of NE in its ubiquitous projection regions have been well studied, but factors controlling activation of NE neurons are less known. The pontine nucleus locus coeruleus (LC) contains the entire population of NE neurons projecting to the forebrain and all cortical and thalamic regions receive NE input. Using single unit recording in freely moving rats, we have been studying neuroanatomical circuits, along with sensory stimuli within their cognitive contexts that control LC firing. Rats are implanted with movable microelectrodes to record activity during a variety of behavioral situations: exploration of novelty in a hole-board, response to tones or odors that predict reward or absence of reward, extinction or reversal of stimulus-reward association. We find that LC-NE neurons respond to novel or salient stimuli, habituate rapidly to respond anew when the stimulus is associated with reward (CS+), particularly in the early stage of learning. Recent experiments suggest that these responses are more related to reward expectancy than to the CS+. Importantly, there is robust LC response to any change in the predictive value of the stimulus, i.e. when new learning must occur. NE released by LC activation will promote the underlying synaptic plasticity.

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